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LANP Long-Acting Natriuretic Peptide

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<strong>LANP</strong><strong>Long</strong>-<strong>Acting</strong> <strong>Natriuretic</strong> <strong>Peptide</strong>Anti-Cancer Effects,Higher Circulating Level than ANP<strong>LANP</strong>, derived from the pro-ANP gene, has been demonstrated to have potentanti-cancer effects. It also has a longer half-life than ANP.<strong>LANP</strong> is also known as <strong>Long</strong>-<strong>Acting</strong> <strong>Natriuretic</strong> <strong>Peptide</strong>, LANH, LANF, ANP(1-30) or Prepro ANP (26-55)<strong>LANP</strong> RIA Standard CurveRK-005-191.210.8B/Bo0.60.4<strong>Natriuretic</strong> peptides we offer that havedemonstrated anti-cancer effects include:alpha-ANP (ANP 1-28) Cat # 005-06Kaliuretic <strong>Peptide</strong> (ANP 104-123) Cat # 005-22<strong>LANP</strong> (ANP 26-55) Cat # 005-19Vessel Dilator (ANP 56-92) Cat # 005-200.201.00 10.00 100.00 1000.00<strong>LANP</strong> (pg/mL)


page 2 Phoenix Pharmaceuticals, Inc. <strong>LANP</strong>Elimination of up to 80% of human pancreatic adenocarcinomas in athymicmice by cardiac hormones.BACKGROUND: Four cardiac hormones have anticancer effects in vitro: i) atrial natriuretic peptide(ANP), ii) vessel dilator, iii) long acting natriuretic peptide (<strong>LANP</strong>), and iv) kaliuretic peptide.MATERIALS AND METHODS: These cardiac hormones were infused subcutaneously for 28 dayswith weekly fresh hormones at 3 nM min(-1) kg(-1) body weight in athymic mice bearing humanpancreatic adenocarcinomas. RESULTS: ANP, vessel dilator, <strong>LANP</strong> and kaliuretic peptide eliminated80%, 33%, 20% and 14% of the pancreatic adenocarcinomas. Even in the treated animals whichdid not have a total cure, their tumor volume decreased to less than 10% (and with vessel dilatorto 2%) of that of the untreated animals. The natriuretic peptide receptor (NPR)-A receptor wasdecreased 33% to 55% in the metastatic lesions compared to the primary pancreatic adenocarcinoma.CONCLUSION: Four cardiac hormones eliminated up to 80% of human pancreatic adenocarcinomasin athymic mice.David L Vesely, Ehrentraud J Eichelbaum, et al. In Vivo. ;21 (3):445-51 17591353 (P,S,E,B)Immunoperoxidase localization of vessel dilator, longactingnatriuretic peptide (<strong>LANP</strong>) [Rabbit Anti-<strong>LANP</strong>/ANP, Prepro (26-55) (Human)Cat. No.: H-005-19], kaliureticpeptide [Rabbit Anti-Atrial <strong>Natriuretic</strong> <strong>Peptide</strong>(ANP) (104-123)-Prepro (Human), Cat. No.: H-005-22] ,and atrial natriuretic peptide (ANP) [Rabbit Anti-Alpha-ANP (1-28) (Human) Antibody, Cat. No.: H-005-06]within human pancreatic adenocarcinomas with each ofthese peptide hormones strongly localizing to cytoplasm(Cy), nucleus (N), endothelium (E), and fibroblasts (F).The light blue stain in the fibroblasts is the nuclei of thefibroblasts. (A) Vessel dilator treated, (B) <strong>LANP</strong> treated,(C) kaliuretic peptide treated, and (D) ANP treated.Primary antibody of each peptide was diluted 1:800.Original magnification x60. The inset in (A) is an isolatednuclei illustrating that vessel dilator has immunoperoxidasestaining within the nucleus. The inset in (D) is anegative control using the human pancreatic adenocarcinomawith substitution of the primary antibodies withnormal rabbit serum.


<strong>LANP</strong>Phoenix Pharmaceuticals, Inc.page 3Immunoperoxidase local ization of vessel dilator[Rabbit Anti-Atrial <strong>Natriuretic</strong> <strong>Peptide</strong> (ANP) (56-92)-Prepro (Human) Antibody, Cat.No. H-005-20]withinthe kid ney demonstrating staining through out thekidney but of increased intensity of staining in theproximal tubules (T) of this normal rat kidney. Originalmagnification x60. Primary antibody diluted 1:800Vessel dilator immunoperoxidase staining in the ratkidney reveals strong staining of the sub-brush borderof proximal convoluted tubules (arrowheads in A andB), including a proximal tubule (A) originating directlyfrom the top left portion of the glomerulus. The interstitialartery (C) had strong proANP-(31—67) staining ofthe elastica with moderate staining of endothelial cells(arrow) and media (*). The distal tubules and collectingducts (arrows in A and B) had weak staining with nodemonstrable staining in some of the collecting ductcells.Cardiac natriuretic peptides: hormones with anticancer effects that localize to nucleus,cytoplasm, endothelium, and fibroblasts of human cancers.Four cardiac peptide hormones, i.e., vessel dilator, long acting natriuretic peptide (<strong>LANP</strong>), kaliureticpeptide, and atrial natriuretic peptide (ANP) synthesized by the same gene decrease within24 hours up to 97% the number of human breast, colon, pancreatic, and prostate adenocarcinomacells as well as human small-cell and squamous carcinomas of the lung cells. These peptide hormonescompletely inhibit the growth of human pancreatic adenocarcinomas growing in athymicmice. Immunocytochemical investigations have revealed that <strong>LANP</strong>, vessel dilator, kaliuretic peptideand ANP localize to the nucleus and cytoplasm of human pancreatic adenocarcinomas, whichis consistent with their ability to decrease DNA synthesis in the nucleus of this cancer mediated bythe intracellular messenger cyclic GMP. These peptide hormones also localize to the endotheliumof capillaries and fibroblasts within these cancers. These are the first growth-inhibiting peptidehormones ever demonstrated to localize to the nucleus. Their ability to decrease the activation ofgrowth promoting substances such as Extracellular Receptor Kinase (ERK)-1/2 and Nuclear FactorKappa Beta (NFkappaB) suggests that in addition to inhibiting DNA synthesis their ability to decreasethe activation of growth promoting substances helps to mediate their ability to inhibit thegrowth of human cancers.Saba SR, Vesely DL. Eur J Clin Invest. 2005 Jun;35(6):388-98


page 4 Phoenix Pharmaceuticals, Inc. <strong>LANP</strong>Amino acid sequences of the natriuretic peptides.Each of the sequences are the human sequences except forDendroaspis natriuretic peptide (DNP), whose sequence isonly known in the snake. The brackets illustrate the location ofcystine bridges that help to form a ring structure in a numberof these peptides. BNP, brain natriuretic peptide; CNP, C-typenatriuretic peptide.David L. Vesely Am J Physiol Renal Physiol 285: F167-F177,2003


<strong>LANP</strong> Phoenix Pharmaceuticals, Inc. Page 5


Page 6Phoenix Pharmaceuticals, Inc.<strong>LANP</strong>Four cardiac hormones eliminate upto 82% of human medullary thyroidcarcinoma cells within 24 hours.Four cardiac hormones, i.e., atrial natriuretic peptide,vessel dilator, long-acting natriuretic peptide,and kaliuretic peptide, which have anticancereffects, were evaluated for the first time on anyendocrine cancer to determine if they have anticancereffects in an endocrine cancer. These fourcardiac hormones were evaluated for their anticancer,DNA synthesis, and receptor status in humanmedullary thyroid cancer cells. There was asignificant (p < 0.001) decrease in human medullarythyroid cancer cells with each 10-fold increasefrom 1 to 100 muM of the four cardiac hormones.There was an 81%, 68%, 71%, and 66% eliminationwithin 24 h of medullary thyroid cancer cellssecondary to vessel dilator, kaliuretic peptide, atrialnatriuretic peptide, and long-acting natriureticpeptide, respectively (p < 0.0001). Three daysafter treatment with these peptide hormones,there was no proliferation of the medullary thyroidcancer cells. These cardiac hormones decreasedDNA synthesis in the medullary thyroid cells from65% to 84% (p < 0.0001). Western blots revealednatriuretic peptide receptors-A and -C werepresent in human medullary thyroid cancer cells.These results indicate the four cardiac hormoneshave potent anticancer effects by eliminating upto 82% of human medullary thyroid carcinomacells within 24 h of treatment.Endocrine. 2006 Dec ;30 (3):325-32 17526945(P,S,E,B)Ehrentraud J Eichelbaum, Brian A Vesely, et al


<strong>LANP</strong> Phoenix Pharmaceuticals, Inc. Page 7


Page 8Phoenix Pharmaceuticals, Inc.<strong>LANP</strong>Catalog# Product Name Std Size005-18 Urodilatin / ANP (95-126) / CDD 200 µgRK-005-18 Urodilatin / ANP (95-126) - RIA Kit 1 kitG-005-18 Urodilatin / ANP (95-126) - Purified IgG Antibody 400 µgT-G-005-18 Urodilatin / ANP (95-126) - I-125 Labeled Purified IgG 10 µCiT-005-18 Urodilatin / ANP (95-126) - I-125 Labeled 10 µCiH-005-18 Urodilatin / ANP (95-126) - Antibody for Immunohistochemistry 50 µlMRK-005-18 Urodilatin (ANP (95-126)) - Magnetic Bead RIA kit 1 kitRK-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - RIA Kit 1 kitG-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - Purified IgG Antibody 400 µgT-G-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - I-125 Labeled Purified IgG 10 µCiT-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - I-125 Labeled 10 µCiEK-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - EIA Kit 1 kitB-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - Biotin Labeled 100 µgH-005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) - Antibody for Immunohistochemistry 50 µl005-19 <strong>LANP</strong> / ANP (26-55), prepro (Human) 200 µg005-39 Auriculin B / ANP (126-150) (Rat) 1 mg005-38 Auriculin A / ANP (126-149) (Rat) 200 µg005-37 Atriopeptin III Analog / PL-058 200 µg005-36 Atriopeptin III (Rat, Mouse, Rabbit) 200 µg005-34 Atriopeptin II (Rat, Mouse, Rabbit) 200 µg005-32 Atriopeptin I (Rat, Mouse, Rabbit) 200 µgPG-H-005-06Atrial <strong>Natriuretic</strong> <strong>Peptide</strong>-Alpha (&#945;-ANP) (1-28) (Human, Ovine, Canine)from Guinea Pig - Antibody for Immunohistochemistry005-14 Atrial <strong>Natriuretic</strong> <strong>Peptide</strong>, Beta (Beta-ANP) (Dimer, Antiparallel) (Human) 100 µg005-05 ANP-30 (Frog) 200 µg005-04 ANP-24 (Frog) 200 µg005-03 ANP-21 (Frog) 200 µgRK-005-14 ANP, beta (Human) - RIA Kit 1 kit005-01 ANP, alpha (Chicken) 200 µgB-005-07 ANP, alpha (1-28) [Di-Biotinyl-Lys] (Human, Ovine, Canine) - Biotin Labeled 100 µgRK-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - RIA Kit 1 kitFR-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Rhodamine Labeled 1 nmolG-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Purified IgG Antibody 400 µgT-G-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - I-125 Labeled Purified IgG 10 µCiT-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - I-125 Labeled 10 µCiFEK-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Fluorescent EIA Kit 1 kitFG-005-06A ANP, alpha (1-28) (Human, Ovine, Canine) - FAM Labeled 1 nmolEK-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - EIA Kit 1 kitFC5-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Cy5 Labeled 1 nmolFC3-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Cy3 Labeled 1 nmolB-G-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Biotin Labeled Purified IgG 100µlH-005-06 ANP, alpha (1-28) (Human, Ovine, Canine) - Antibody for Immunohistochemistry 50 µl005-06 ANP, alpha (1-28) (Human, Ovine, Canine) 200 µgG-005-14 ANP, &#946; (Human) - Purified IgG Antibody 400 µgT-G-005-14 ANP, &#946; (Human) - I-125 Labeled Purified IgG 10 µCiT-005-14 ANP, &#946; (Human) - I-125 Labeled 10 µCiH-005-14 ANP, &#946; (Human) - Antibody for Immunohistochemistry 50 µlRK-005-24 ANP (Rat, Mouse) - RIA Kit 1 kit50 µl


<strong>LANP</strong> Phoenix Pharmaceuticals, Inc. Page 9FR-G-005-24 ANP (Rat, Mouse) - Rhodamine Labeled Purified IgG 100 µlFR-005-24 ANP (Rat, Mouse) - Rhodamine Labeled 1 nmolG-005-24 ANP (Rat, Mouse) - Purified IgG Antibody 400 µgMRK-005-24 ANP (Rat, Mouse) - Magnetic Bead RIA kit 1 kitT-G-005-24 ANP (Rat, Mouse) - I-125 Labeled Purified IgG 10 µCiT-005-24 ANP (Rat, Mouse) - I-125 Labeled 10 µCiFG-G-005-24A ANP (Rat, Mouse) - FAM Labeled Purified IgG 100 µlFG-005-24A ANP (Rat, Mouse) - FAM Labeled 1 nmolEK-005-24 ANP (Rat, Mouse) - EIA Kit 1 kitB-G-005-24 ANP (Rat, Mouse) - Biotin Labeled Purified IgG 100 µlB-005-24 ANP (Rat, Mouse) - Biotin Labeled 100 µgH-005-24 ANP (Rat, Mouse) - Antibody for Immunohistochemistry 50 µl005-24 ANP (Rat, Mouse) 200 µg005-02 ANP (Eel) 200 µg005-28 ANP (8-33) (Rat) 200 µg005-13 ANP (7-28) (Human, Ovine, Canine) 200 µg005-45 ANP (7-23) (Human) 200 µgT-005-20 ANP (56-92), Prepro [Tyr0] (Human) - I-125 Labeled 10 µCiRK-005-20 ANP (56-92), Prepro (Human) - RIA Kit 1 kitG-005-20 ANP (56-92), Prepro (Human) - Purified IgG Antibody 400 µgT-G-005-20 ANP (56-92), Prepro (Human) - I-125 Labeled Purified IgG 10 µCiH-005-20ANP (56-92), Prepro (Human) - Antibody for Immunohistochemistry50 µl005-20 ANP (56-92), Prepro (Human) 200 µgFG-005-12A ANP (5-28) (Human, Ovine, Canine) - FAM Labeled 0005-12 ANP (5-28) (Human, Ovine, Canine) 200 µg005-11 ANP (5-27) (Human, Ovine, Canine) 200 µg005-10 ANP (4-28) (Human, Ovine, Canine) 200 µg005-26 ANP (4-23)-Amide Des-[Gln18, Ser19, Gly20, Leu21,Gly22] (Rat)200 µg005-46 ANP (104-126) Des-[Cys105, Cys121] (Rat) 200 µgT-005-25 ANP (104-123), Prepro [Tyr0] (Human) - I-125 Labeled 10 µCi005-25 ANP (104-123), Prepro [Tyr0] (Human) 100 µgRK-005-22 ANP (104-123), Prepro (Human) - RIA Kit 1 kitG-005-22 ANP (104-123), Prepro (Human) - Purified IgG Antibody 400 µgT-G-005-22H-005-22ANP (104-123), Prepro (Human) - I-125 Labeled PurifiedIgGANP (104-123), Prepro (Human) - Antibody for Immunohistochemistry10 µCi50 µl005-22 ANP (104-123), Prepro (Human) 200 µgT-005-23 ANP (104-116), Prepro [Tyr0] (Human) - I-125 Labeled 10 µCi005-23 ANP (104-116), Prepro [Tyr0] (Human) 100 µgRK-005-21 ANP (104-116), Prepro (Human) - RIA Kit 1 kitG-005-21 ANP (104-116), Prepro (Human) - Purified IgG Antibody 400 µgT-G-005-21H-005-21ANP (104-116), Prepro (Human) - I-125 Labeled PurifiedIgGANP (104-116), Prepro (Human) - Antibody for Immunohistochemistry10 µCi50 µl005-21 ANP (104-116), Prepro (Human) 200 µgMRK-005-06ANP (1-28) Alpha (Human, Ovine, Canine) - MagneticBead RIA kit1 kit

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